Pituitary deficiency after brain radiation therapy.

Brain radiotherapy is a frequent and overlooked cause of pituitary deficiency in adults which may alter patients' health and quality of life. Hormonal consequences have been better studied in children. The onset of hormonal deficiencies depends on the dose delivered to the pituitary-hypothalamic region while their incidence and severity depends on dose fractionating and follow-up duration. Somatotrophic function is the first affected, 90% of patients being GH deficient 10 years after radiotherapy. Other anterior pituitary functions are affected later and less frequently. While initial damage occurs in the hypothalamus, accounting for mild hyperprolactinemia in 30-50% of cases, diabetes insipidus is never observed. Direct pituitary deficiency may occur later. Responses to ACTH or GHRH-arginine tests may be normal for several years though an ACTH and/or GH deficiency has been demonstrated by an insulin tolerance test, which is considered as the gold standard. When the cranio-spinal area--including the neck--has been irradiated, primary thyroid deficiency might occur. Repeated cervical ultrasonographic follow-up is mandatory to exclude radiation-induced thyroid cancer. The gonadotrophic function might be altered after small doses of irradiation causing precocious puberty, while at higher doses delayed puberty or true gonadotrophic deficiencies are more often observed. Combined radio- and chemotherapy might result in mixed central and peripheral deficiencies that might be difficult to diagnose. When radiotherapy is performed in adulthood, GH deficiency is less common, although the sequence of hormonal deficiencies is similar to that observed in children. Prospective longitudinal studies are required to determine the time course and sequence of onset of each deficiency, in order to tailor the monitoring of these patients to their specific needs.